title: Flagellin/TLR5 signaling potentiates airway serous secretion from swine tracheal submucosal glands.
abstract: Airway serous secretion is essential for the maintenance of mucociliary transport in airway mucosa, which is responsible for the upregulation of mucosal immunity. Although there are many articles concerning the importance of Toll-like receptors (TLRs) in airway immune systems, the direct relationship between TLRs and airway serous secretion has not been well investigated. Here, we focused on whether TLR5 ligand flagellin, which is one of the components of Pseudomonas aeruginosa, is involved in the upregulation of airway serous secretion. Freshly isolated swine tracheal submucosal gland cells were prepared, and the standard patch-clamp technique was applied for measurements of the whole cell ionic responses of these cells. Flagellin showed potentiating effects on these oscillatory currents induced by physiologically relevant low doses of acetylcholine (ACh) in a dose-dependent manner. These potentiating effects were TLR5 dependent but TLR4 independent. Both nitric oxide (NO) synthase inhibitors and cGMP-dependent protein kinase (cGK) inhibitors abolished these flagellin-induced potentiating effects. Furthermore, TLR5 was abundantly expressed on tracheal submucosal glands. Flagellin/TLR5 signaling further accelerated the intracellular NO synthesis induced by ACh. These findings suggest that TLR5 takes part in the airway mucosal defense systems as a unique endogenous potentiator of airway serous secretions and that NO/cGMP/cGK signaling is involved in this rapid potentiation by TLR5 signaling.
authors.affiliation: Dept. of Respiratory Medicine, Tohoku Univ. Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, JAPAN. tamada@rm.med.tohoku.ac.jp.
authors.forename: Soshi
authors.initials: S
authors.lastname: Muramatsu
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Tamada
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nara
authors.forename: Koji
authors.initials: K
authors.lastname: Murakami
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kikuchi
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kanehira
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Maruyama
authors.forename: Masahito
authors.initials: M
authors.lastname: Ebina
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nukiwa
authors.forename: Masakazu
authors.initials: M
authors.lastname: Ichinose
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology / Q000502:physiology; D061354:Acinar Cells / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001834:Body Water / Q000378:metabolism; D020013:Calcium Signaling; D018679:Cholinergic Agonists / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D005088:Exocrine Glands / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D005408:Flagellin / Q000276:immunology*; D008564:Membrane Potentials; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D034421:Sus scrofa; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D051198:Toll-Like Receptor 5 / Q000378:metabolism*; D014132:Trachea / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
chemical_list: D018679:Cholinergic Agonists; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5; D005408:Flagellin; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP; D000109:Acetylcholine
keywords: Ca2+-activated Cl- channel; Pseudomonas aeruginosa; cGMP-dependent protein kinase; nitric oxide; patch-clamp